rs3734966

chr7-155070724-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024012.4(HTR5A):c.-176T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 687,090 control chromosomes in the GnomAD database, including 4,970 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1962 hom., cov: 33)
  • Exomes 𝑓: 0.095 (3008 hom.)
• Consequence: HTR5A NM_024012.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

Genes affected

HTR5A (HGNC:5300): (5-hydroxytryptamine receptor 5A) The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects. The gene described in this record is a member of 5-hydroxytryptamine (serotonin) receptor family and encodes a multi-pass membrane protein that functions as a receptor for 5-hydroxytryptamine and couples to G-proteins. This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization. [provided by RefSeq, Jul 2008]

HTR5A-AS1 (HGNC:48956): (HTR5A antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR5A	NM_024012.4	c.-176T>C		5_prime_UTR_variant	1/2	ENST00000287907.3
HTR5A-AS1	NR_038945.1	n.524+310A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR5A	ENST00000287907.3	c.-176T>C		5_prime_UTR_variant	1/2	1	NM_024012.4	P1
HTR5A-AS1	ENST00000671665.1	n.1417+310A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21125 AN: 151922 Hom.: 1957 Cov.: 33

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0805

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0951 AC: 50871 AN: 535050 Hom.: 3008 Cov.: 6 AF XY: 0.0937 AC XY: 26299 AN XY: 280678

Gnomad4 AFR exome AF: 0.264

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.0946

Gnomad4 FIN exome AF: 0.0780

Gnomad4 NFE exome AF: 0.0753

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.139 AC: 21173 AN: 152040 Hom.: 1962 Cov.: 33 AF XY: 0.139 AC XY: 10305 AN XY: 74314

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0805

Gnomad4 NFE AF: 0.0750

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0981 Hom.: 902

Bravo AF: 0.154

Asia WGS AF: 0.128 AC: 445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	4.4
Dann	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3734966; hg19: chr7-154862434; COSMIC: COSV55283870; COSMIC: COSV55283870;